This proposed research will refine and prospectively validate the effectiveness of quantitative ultrasound (QUS) technology [QUS parameters: cervical ultrasound attenuation coefficient (ATTEN), cervical ultrasound backscatter coefficient (BSC)], when compared to ultrasound (US)-estimated cervical length (CL), to identify women at risk for spontaneous preterm birth (sPTB). Preterm birth (PTB) is defined as birth before 37 completed weeks' gestation (wks GA). Annually in the U.S., more than 440,000 infants are born preterm, and over 80,000 are born very preterm (prior to 32 wks). Consequences of PTB for survivors are severe, can be life-long and cost society $30 billion annually, a cost that far exceeds that of any major adult diagnosis. Predicting women at risk for sPTB has been medically challenging due to: 1) lack of signs and symptoms of preterm labor until intervention is too late, and 2) lack of sufficiently sensitive screening tools to signal sPTB risk early enough when an intervention would likely be effective. Spontaneous preterm labor is a syndrome associated with multiple etiologies of which only a portion may be associated with cervical insufficiency; however, regardless of the etiology of PTB, the cervix must remodel for passage of the fetus. Novel QUS technology has been developed by our multidisciplinary investigative team and shows promise for becoming a widely available and useful method for early detection of sPTB. QUS technology is a feature that can readily be added to current clinical ultrasound systems, thereby reducing the time from basic science innovation translation to improve clinical care of women. Our pilot studies show that women who experienced sPTB have a significantly lower ATTEN at 20 wks GA (relative to full-term women at 20 wks), and ATTEN at 20 wks more accurately predicts sPTB than CL at 24 wks. When both ATTEN and CL measures are combined, sPTB prediction is improved. Our goals are to identify: 1) women at risk for sPTB earlier and with better accuracy than with CL alone, and 2) differences between women who do/do not respond to progestogen therapy. To achieve these goals, we propose to quantify ATTEN, BSC & CL at two time points (202 & 242 wks GA; each exam separated by 4 wks) to identify individuals at greatest risk of sPTB. Our pilot data identified 202 wks to be sensitive to ATTEN differences and 242 wks to be sensitive to CL differences. Three groups of women will be recruited: 1) prior sPTB, 2) short CL at 20 wks, and 3) low-risk control group. Central hypothesis: Cervical ATTEN & BSC (alone or combined) at 202 wks are better than CL at 242 wks for detecting risk of sPTB; further, ATTEN, BSC & CL at 202 & 242 wks, when combined, are even better for detecting risk of sPTB.